JERUSALEM--(BUSINESS WIRE)--Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) today announced that results from the 52-week, multicenter, randomized, double-blind, parallel group study evaluating monthly or quarterly AJOVY® (fremanezumab-vfrm) injection in adults with chronic migraine (CM) or episodic migraine (EM), were published online ahead of print in Neurology.
“Migraine can be a difficult disease to treat, and is often debilitating for those who suffer from it,” said Denisa Hurtukova, MD, Vice President, Head of North America Medical Affairs, Teva. “We are pleased to publish these results, which add to the growing body of knowledge on AJOVY and give us further insight into the potential for AJOVY to improve clinical outcomes with both quarterly and monthly dosing regimens. These results also underscore Teva’s commitment to patients with migraine and providing potential long-term treatment options for this debilitating disease.”
As the primary purpose of the study was the collection of long-term safety data for patients treated with AJOVY, the study was not placebo-controlled. Patients and investigators were both blinded to the dosing regimen (quarterly vs. monthly) to allow for comparisons between the two dosing options. The study was conducted between March 2016 and December 2018, and included 1890 patients with CM (1,110) and EM (780). Patients who completed either the HALO CM or HALO EM trials had the option to roll over to this long-term study, and new patients could also be enrolled. A total of 312 patients were newly enrolled. Patients were studied at 135 sites, which included clinical research centers, academic medical centers, and neurology/headache practices in the US, Japan, Czech Republic, Russia, Canada, Finland, Poland, Israel, and Spain.
The primary objective of the study was to observe the long-term safety and tolerability of AJOVY over 52 weeks. The most common adverse events (AEs) leading to discontinuation (3-5 percent of patients) included injection site erythema, injection site rash, injection site swelling, injection site pruritis and increased weight. No clinically significant patterns of AEs or serious AEs were seen in the current study. No treatment-emergent, clinically significant laboratory findings were observed.
“Patients with migraine have difficulty remaining on many migraine preventive therapies for prolonged periods and persistence rates at 6 months are known to be quite low, with literature citing lack of efficacy and adverse events as the most common reasons for discontinuation,” said Peter J. Goadsby, MD, PhD, NIHR-Wellcome Trust King's Clinical Research Facility, SLaM Biomedical Research Centre, King's College London, London, UK. “The low rates of discontinuation in this 12 month extension study due to lack of efficacy (4 percent of patients) or adverse events (3-5 percent of patients) suggest the potential that patients may be able to persist with this medication over a clinically relevant length of time.”
Although the study was not placebo-controlled, exploratory efficacy evaluations included mean change from baseline in the monthly number of migraine days, headache days of at least moderate severity, headache days of any severity, and days with any acute headache medication use at months three, six, and 12. Additionally, for patients with CM, mean change from baseline in headache-related disability score at months six and 12 was measured by the six-item Headache Impact Test (HIT-6) and for patients with EM, the mean change from baseline in headache-related disability score at months six and 12 was measured by the Migraine Disability Assessment (MIDAS) questionnaire.
In patients with CM or EM, the monthly number of migraine days decreased from baseline to month 12 (CM quarterly, –7.2 days; CM monthly, – 8.0 days; EM quarterly, –5.2 days; EM monthly, –5.1 days). Reductions in monthly number of headache days of at least moderate severity from baseline to month 12 were observed (CM quarterly, –6.4 days; CM monthly, –6.8 days; EM quarterly, –4.4; EM monthly, –4.2 days). Monthly number of headache days of any severity and monthly number of days of any acute headache medication use were also reduced across all treatment groups. More than half of patients with CM and approximately two-thirds of patients with EM had a ≥ 50 percent reduction in monthly average number of migraine days from baseline to month 12. Specifically, the proportions of patients who had a ≥ 50 percent response rate continued to increase over time. Additionally, the degree of headache-related disability decreased for both CM and EM patients from baseline to month 12.
About the HALO Clinical Research Program
The Phase III HALO EM and CM studies were 16-week, multicentre, randomised, double-blind, placebo-controlled, parallel-group studies to compare the safety, tolerability, and efficacy of four dose regimens (two for EM [quarterly and monthly] and two for CM [quarterly and monthly]), of subcutaneous fremanezumab compared to placebo in adults with episodic and chronic migraine. The studies consisted of a screening visit, a 28-day run-in period, and a 12-week (84-day) treatment period, including a final evaluation at week 12 (end-of-treatment [EOT] visit, four weeks [28 days] after the final dose of study drug).
- In the EM study, 875 patients were enrolled (294, 291, 290 patients in the placebo, quarterly, and monthly dose groups, respectively). Patients were randomised in a 1:1:1 ratio to receive subcutaneous injections of fremanezumab at 225 mg for three months (monthly dose regimen), fremanezumab at 675 mg at initiation followed by placebo for two months (quarterly dose regimen), or three monthly doses of matching placebo. The primary efficacy endpoint of the EM study was the mean change from baseline (28-day run-in period) in the monthly average number of migraine days during the 12-week period after the first dose of fremanezumab.
- In the CM study, 1,130 patients were randomised (375, 376, 379 patients in the placebo, quarterly, and monthly groups, respectively). Patients were randomised in a 1:1:1 ratio to receive subcutaneous injections of fremanezumab at 675 mg at initiation followed by monthly 225 mg for two months (monthly dose regimen), fremanezumab at 675 mg at initiation followed by placebo for two months (quarterly dose regimen), or three monthly doses of matching placebo. The primary efficacy endpoint of the CM study was the mean change from baseline (28-day run-in period) in the monthly average number of headache days of at least moderate severity during the 12-week period after the first dose of fremanezumab.
U.S. Important Safety Information about AJOVY® (fremanezumab-vfrm) injection
Contraindications: AJOVY is contraindicated in patients with serious hypersensitivity to fremanezumab-vfrm or to any of the excipients.
Hypersensitivity Reactions: Hypersensitivity reactions, including rash, pruritus, drug hypersensitivity, and urticaria were reported with AJOVY in clinical trials. Most reactions were mild to moderate, but some led to discontinuation or required corticosteroid treatment. Most reactions were reported from within hours to one month after administration. If a hypersensitivity reaction occurs, consider discontinuing AJOVY and institute appropriate therapy.
Adverse Reactions: The most common adverse reactions (≥5% and greater than placebo) were injection site reactions.
Please click here for full U.S. Prescribing Information for AJOVY® (fremanezumab-vfrm) injection.
Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) has been developing and producing medicines to improve people’s lives for more than a century. We are a global leader in generic and specialty medicines with a portfolio consisting of over 3,500 products in nearly every therapeutic area. Around 200 million people around the world take a Teva medicine every day, and are served by one of the largest and most complex supply chains in the pharmaceutical industry. Along with our established presence in generics, we have significant innovative research and operations supporting our growing portfolio of specialty and biopharmaceutical products. Learn more at www.tevapharm.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, regarding AJOVY®, which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to:
- The commercial success of AJOVY;
- our ability to successfully compete in the marketplace, including: that we are substantially dependent on our generic products; consolidation of our customer base and commercial alliances among our customers; the increase in the number of competitors targeting generic opportunities and seeking U.S. market exclusivity for generic versions of significant products; competition for our specialty products, especially COPAXONE®, our leading medicine, which faces competition from existing and potential additional generic versions, competing glatiramer acetate products and orally-administered alternatives; the uncertainty of commercial success of AJOVY or AUSTEDO®; competition from companies with greater resources and capabilities; delays in launches of new products and our ability to achieve expected results from investments in our product pipeline; ability to develop and commercialize biopharmaceutical products; efforts of pharmaceutical companies to limit the use of generics, including through legislation and regulations and the effectiveness of our patents and other measures to protect our intellectual property rights;
- our substantial indebtedness, which may limit our ability to incur additional indebtedness, engage in additional transactions or make new investments, may result in a further downgrade of our credit ratings; and our inability to raise debt or borrow funds in amounts or on terms that are favorable to us;
- our business and operations in general, including: uncertainty regarding the magnitude, duration, and geographic reach of the COVID-19 pandemic and its impact on our business, financial condition, operations, cash flows, and liquidity and on the economy in general; interruptions in our supply chain, including due to potential effects of the COVID-19 pandemic on our operations and business in geographic locations impacted by the pandemic and on the business operations of our customers and suppliers; adequacy of and our ability to successfully execute and maintain the activities and efforts related to the measures we have taken or may take in response to the COVID-19 pandemic and associated costs therewith; effectiveness of our restructuring plan announced in December 2017; challenges associated with conducting business globally, including adverse effects of the COVID-19 pandemic, political or economic instability, major hostilities or terrorism; our ability to attract, hire and retain highly skilled personnel; our ability to develop and commercialize additional pharmaceutical products; compliance with anti-corruption sanctions and trade control laws; manufacturing or quality control problems; disruptions of information technology systems; breaches of our data security; variations in intellectual property laws; significant sales to a limited number of customers; our ability to successfully bid for suitable acquisition targets or licensing opportunities, or to consummate and integrate acquisitions; our prospects and opportunities for growth if we sell assets and potential difficulties related to the operation of our new global enterprise resource planning (ERP) system;
- compliance, regulatory and litigation matters, including: our ability to successfully defend against the DOJ criminal charges of a Sherman Act violations; increased legal and regulatory action in connection with public concern over the abuse of opioid medications in the U.S. and our ability to reach a final resolution of the remaining opioid-related litigation; costs and delays resulting from the extensive governmental regulation to which we are subject or delays in governmental processing time including due to modified government operations due to the COVID-19 pandemic and effects on product and patent approvals; the effects of reforms in healthcare regulation and reductions in pharmaceutical pricing, reimbursement and coverage; governmental investigations into S&M practices; potential liability for patent infringement; product liability claims; increased government scrutiny of our patent settlement agreements; failure to comply with complex Medicare and Medicaid reporting and payment obligations; and environmental risks;
- other financial and economic risks, including: our exposure to currency fluctuations and restrictions as well as credit risks; potential impairments of our intangible assets; potential significant increases in tax liabilities; and the effect on our overall effective tax rate of the termination or expiration of governmental programs or tax benefits, or of a change in our business;
and other factors discussed in our Quarterly Reports on Form 10-Q for the first and second quarters of 2020 and our Annual Report on Form 10-K for the year ended December 31, 2019, including in the sections captioned "Risk Factors” and “Forward Looking Statements.” Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements.